2020
DOI: 10.1002/humu.24096
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Abstract: Mutations in RBM20 encoding the RNA-binding motif protein 20 (RBM20) are associated with an early onset and clinically severe forms of cardiomyopathies. Transcriptome analyses revealed RBM20 as an important regulator of cardiac alternative splicing. RBM20 mutations are especially localized in exons 9 and 11 including the highly conserved arginine and serine-rich domain (RS domain). Here, we investigated in several cardiomyopathy patients, the previously described RBM20-mutation p.Pro638Leu localized within the… Show more

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Cited by 24 publications
(57 citation statements)
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“…RBM20 is known to localize to the nucleus, where it forms discrete foci that exquisitely co-localize with the site of TTN transcription (Bertero et al, 2019). However, several groups have demonstrated that both RSRSP deletion mutants and DCM point mutations within the RSRSP stretch, including the R636S mutation, result in mis-localization of overexpressed (exogenous) RBM20 from the nucleus to the cytoplasm (Ihara et al, 2020; Schneider et al, 2020; Filippello et al, 2013; Murayama et al, 2018; Sun et al, 2020; Gaertner et al, 2020). Confocal analyses indicated that endogenous RBM20 in WT iPSC-CMs localized to the nucleus and was enriched in prominent foci (usually two per nucleus, as immature iPSC-CMs are generally diploid), while R636S HTZ and R636S HMZ iPSC-CMs displayed more numerous and smaller RBM20 puncta which appeared primarily cytoplasmic ( Fig.…”
Section: Resultsmentioning
confidence: 99%
“…RBM20 is known to localize to the nucleus, where it forms discrete foci that exquisitely co-localize with the site of TTN transcription (Bertero et al, 2019). However, several groups have demonstrated that both RSRSP deletion mutants and DCM point mutations within the RSRSP stretch, including the R636S mutation, result in mis-localization of overexpressed (exogenous) RBM20 from the nucleus to the cytoplasm (Ihara et al, 2020; Schneider et al, 2020; Filippello et al, 2013; Murayama et al, 2018; Sun et al, 2020; Gaertner et al, 2020). Confocal analyses indicated that endogenous RBM20 in WT iPSC-CMs localized to the nucleus and was enriched in prominent foci (usually two per nucleus, as immature iPSC-CMs are generally diploid), while R636S HTZ and R636S HMZ iPSC-CMs displayed more numerous and smaller RBM20 puncta which appeared primarily cytoplasmic ( Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Figure 1 and Table 1 present reported variants with corresponding domains. Most patients carry heterozygous mutations, and the mode of inheritance is autosomal dominant [ 15 ]. Three protein regions were identified with high confidence for carrying pathogenic variants [ 12 , 15 ].…”
Section: Rbm20 Mutations Cause Highly Penetrant Cardiomyopathiesmentioning
confidence: 99%
“…Most patients carry heterozygous mutations, and the mode of inheritance is autosomal dominant [ 15 ]. Three protein regions were identified with high confidence for carrying pathogenic variants [ 12 , 15 ]. These are located at positions c.1601-1640 (exon 7, encoding the RRM-domain), c.1881-1920 (exon 9, encoding the highly conserved RS-domain) and c.2721-2760 (exon 11) [ 12 , 16 , 17 ].…”
Section: Rbm20 Mutations Cause Highly Penetrant Cardiomyopathiesmentioning
confidence: 99%
“…The study protocol was approved by the local ethics committee. DNA isolation and panel sequencing were performed as described previously [51,52]. Briefly, DNA was isolated from blood with the High Pure PCR Template Preparation Kit ® (Roche Diagnostics GmbH, Mannheim, Germany) and used for cardiac gene enrichment re-sequencing on a MiSeq ® next-generation sequencing system according to the manufacturer's instructions (TruSight TM Rapid Capture Preparation Kit; Illumina, San Diego, CA, USA).…”
Section: Genetic Analysesmentioning
confidence: 99%